Amyotrophic lateral sclerosis - Lou Gehrig’s disease

Amyotrophic Lateral Sclerosis (ALS) - also known as the Lou Gehrig´s disease - is one of multiple degenerative motor neuron diseases that are clinically defined, based on the involvement of upper and/or lower motor neurons.
Its clinical hallmark is the combination of:
1. Upper motor neuron signs and symptoms: weakness, hyperreflexia, and spasticity result from degeneration of frontal motor neurons.
2. Lower motor neuron signs and symptoms: weakness, atrophy or amyotrophy, and fasciculations are a direct consequence of degeneration of neurons in the brainstem and spinal cord producing muscle denervation.

The loss of motor neurons results in the primary clinical symptoms and signs of ALS. These may produce impairment affecting limb, bulbar, axial and respiratory function.
- Asymmetric limb weakness is the most common presentation of ALS (80 percent).
- Bulbar ALS onset, usually manifested as dysarthria or dysphagia, is the next most common presentation (20 percent).
- Cognitive impairment, may precede or follow the onset of motor neurons dysfunction in patients with ALS.
- Frontotemporal dementia may be associated with ALS in 15 to 50 percent of cases.
- Autonomic symptoms may occur in ALS as the disease progresses.

Diagnosis. Is made when it is suggested by the history and physical examination, supported by electrodiagnostic studies, and not excluded by neuroimaging and laboratory studies. Neuroimaging is used to exclude other possible diagnoses in the evaluation of suspected ALS.

ALS is an incurable and progressive illness that leads inexorably to death; median survival after symptom onset is 30 months, but the range is anywhere from months to decades.

Management of common symptoms.

Sialorrhea. Bulbar weakness, spasticity, and loss of muscle control in ALS can lead to dysphagia which causes difficulty swallowing one’s saliva. This condition, secretions aspiration perioral skin irritation
Pharmacologic management strategies
- Medications that inhibit saliva production, such as atropine, glycopyrrolate, tricyclic anti-depressants, and scopolamine patches. These medications capitalize on the anti-cholinergic side effect of xerostomia; therefore, other less desirable anti-cholinergic side effects such as constipation, urinary retention, and cognitive dysfunction are a risk.
- Botulinum toxin A and B injections into salivary glands; the toxin reduces the production of saliva by inhibiting the release of acetylcholine at neurosecretory junctions within the salivary glands.
Non-pharmacologic management strategies.
- Portable suction devices can be used to clear excess secretions.
- Unilateral salivary gland irradiation.
- In rare cases, laryngectomy is used for secretion management and prevention of aspiration in patients whose speech is already severely compromised

Pseudobulbar Affect (PBA) - disordered emotional expressions caused by disruption of cortico-pontine-cerebellar tracts; It typically manifests as inappropriate and uncontrollable laughing or crying inconsistent with the patient’s mood and can be socially debilitating.
- Combination drug dextromethorphan/quinidine - its mechanism of action seems to be related to its anti-glutamatergic and anti-NMDA actions. The recommended dose is 20 mg dextromethorphan/10 mg quinidine twice daily.
- Tricyclic and SSRI anti-depressants have shown benefit.

Depression. Major depressive disorder is a common in ALS; selective serotonin reuptake inhibitors are often used.

Spasticity. Damage to the upper motor neurons in ALS leads to spasticity, which can be associated with cramps and incoordination of movement.
- Baclofen: initial dosing is 5-10 mg BID-TID; doses up to 120 mg per day may be needed.
- Tizanidine: initial dosing is 2-4 mg BID with 24 mg as the maximum daily dose.
- Intrathecal baclofen pumps are considered only for patients with medically refractory spasticity.

Pain. Spasticity, muscle spasms, joint stiffness and skin breakdown related to immobility are all potential sources of pain in ALS, which occurs in the later stages in up to 80% of patients. Non-opioid analgesics and anti-inflammatory medications are generally considered first-line; when these medications fail, opioids are used commonly.

Dyspnea. Ventilatory failure is common in the later stages of ALS, occurring in up to 85% of patients. In addition to non-invasive ventilation, opioids are used commonly to relieve dyspnea.

Riluzole is is the only proven disease-modifying pharmacologic agent in ALS, providing a modest survival benefit of 2-3 months and likely works via inhibition of glutamate release.

Head drop. Axial muscle involvement, particularly neck extensor can lead to disabling head drop and kyphosis. A soft collar, a semi-rigid collar and adjustable head rests on wheelchairs may be needed.

Dysphagia. It is a common bulbar manifestation of ALS and should be assessed each visit. Poor nutritional status at diagnosis or disease progression has been associated with higher mortality.
Early referrals to a dietitian and speech pathologist are recommended. Use of thickened fluids, high-protein/high-calorie supplements, and modified swallowing techniques can mitigate the malnutrition associated with dysphagia.Gastrostomy tubes do not prevent aspiration, but they have been shown to improve nutritional status and may prolong survival. It is highly recommended that if patients are agreeable to getting a gastronomy tube, it be done before vital capacity falls below 50% of predicted.
Nasogastric tubes have been used as a short-term alternative, but they are uncomfortable and may worsen sialorrhea.

Ventilatory compromise. The most common cause of death in ALS is ventilatory failure. Symptoms of ventilatory compromise, such as poor nighttime sleep, daytime somnolence, anorexia, morning headache, and weak cough, often precede dyspnea.
- Noninvasive ventilation with bilevel positive airway pressure has been shown to prolong survival and improve quality of life in patients with ALS who can maintain their airway.
- Nasal masks/pillows and sip/puff devices may improve tolerability.
- Mechanical in-exufflators alternate positive and negative pressures to improve airflow and clearance of secretions.
- Diaphragmatic pacemakers can be surgically implanted to stimulate more forceful muscle contractions in patients with some degree of residual diaphragm function.

Impairment of mobility. Physical therapy and use of equipment such as canes, walkers, and ankle-foot orthoses can minimize foot-drop, improve gait, and help prevent falls. Occupational therapy with assistive devices such as modified cutlery, Velcro fasteners for dressing, and bathroom modifications such as grab bars and higher toilet seats help maintain function. In patients with prominent distal weakness, wrist braces at 30 to 35 degrees can improve grip efficiency while a universal cuff can assist with eating and typing. Early intermittent use of a wheelchair is recommended for energy conservation.

Riluzole is is the only proven disease-modifying pharmacologic agent in ALS, providing a modest survival benefit of 2-3 months and likely works via inhibition of glutamate release.

Impairment of communication. Computer, tablet, or smartphone applications can be used to generate electronic speech from typed language.

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